F. M. Singer et al., "New Inhibitors of in vitro Conversion of Acetate and Mevalonate to Cholesterol", Proc. Soc. Exper. Biol. Med., 102, 370 (1959) and F. H. Hulcher, "Inhibition of Hepatic Cholesterol Biosynthesis by 3,5-Dihydroxy-3,4,4,-trimethylvaleric Acid and its Site of Action," Arch. Biochem. Biophys., 146, 422 (1971) disclose that certain mevalonate derivatives inhibit the biosynthesis of cholesterol.
Singer et al. reported that fluoromevalonic acid is more effective in inhibiting biosynthesis of cholesterol (as measured by in vitro conversion of labeled acetate and labeled mevalonate into cholesterol) than .DELTA.4-androstene-17.alpha.-ol-3-one-17.beta.-oic acid and .DELTA.1-testololactone.
Hulcher reported that an analog of mevalonic acid (3,5-dihydroxy-3,4,4-trimethylvaleric acid) strongly inhibits cholesterol biosynthesis by rat liver homogenates.
U.S. Pat. No. 3,983,140 to Endo et al. discloses the fermentation product ML-236B, referred to generically as compactin and mevastatin, which has the structure ##STR2## This compound is prepared by cultivation of a microorganism of the genus Penicillium. The fermentation process is disclosed in U.S. Pat. No. 4,049,495 issued Sep. 20, 1977 to Endo et al.
Brown, A. G., et al., (Beecham Pharmaceuticals Research Div.), "Crystal and Molecular Structure of Compactin, a New Antifungal Metabolite from Penicillium Brevicompactum", J. Chem. Soc. Perkin I. 1165-1170 (1976) confirms that compactin has the complex mevalonolactone structure disclosed by Endo et al. in the above patents.
U.S. Pat. No. 4,231,938 to Monaghan et al. discloses mevinolin (also called lovastatin, Monacolin K, and MK-803), which has the structure ##STR3## This compound is prepared by culturing a microorganism of the genus Aspergillus.
U.S. Pat. No. 4,346,227 to Terahara et al. discloses pravastatin, which has the structure ##STR4##
Pravastatin is prepared by the enzymatic hydroxylation of compactin or its carboxylic acid, as disclosed in U.S. Pat. No. 4,410,629 to Terahara et al.
U.S. Pat. No. 4,448,979, issued May 15, 1984 to Terahara et al., discloses the lactone of pravastatin.
U.S. Pat. Nos. 4,444,784 and 4,450,171 to Hoffman et al disclose various antihypercholesterolemic compounds, including synvinolin (simvastatin), which has the structure ##STR5## The Hoffman patents further disclose compounds of the structures ##STR6## wherein R.sup.1 is H or CH.sub.3, R can be an alkyl group including ##STR7## X, Y and Z are single and/or double bonds in all possible combinations.
European Patent Application 0065835A1, filed by Sankyo, discloses cholesterol biosynthesis-inhibiting compounds of the structure ##STR8##
The same application discloses the corresponding free carboxylic acids, which may be represented by the formula ##STR9## in which one of R.sup.1 and R.sup.2 represents a hydrogen atom and the other represents a hydroxy group. The Sankyo application further discloses salts and esters of the carboxylic acids.